Human retroviruses are emerging as etiologic agents of human malignancies. HTLV-I is linked to adult T-cell leukemia (ATL). HTLV-III/LAV, the etiologic agent of the acquired immunodeficiency syndrome (AIDS), is associated with Kaposi's sarcoma and certain forms of Hodgkin's and non-Hodgkin's lymphoma. Our research is focused on characterizing the relationship of this class of virus to human malignancy. Results of our studies document the spectrum of ATL and modes of spread of HTLV-I by heterosexual and homosexual contact and suggest early life transmission in the household. An indirect etiologic mechanism of carcinogenesis is also suggested for HTLV-I in B-cell chronic lymphocytic leukemia (B-CLL), and for HTLV-III/LAV in studies of Hodgkin's and non-Hodgkin's lymphoma and Kaposi's sarcoma. A major focus of HTLV-III/LAV research has been on cohorts at high-risk for AIDS followed longitudinally since the very beginning of the AIDS epidemic. Results of these studies have documented major modes of transmission of HTLV-III/LAV in homosexual men (via receptive anal intercourse with multiple partners in high-risk areas), in hemophiliacs (via commercial plasma products), and in drug users (via frequent needle injections). They have also documented the progression from seroconversion to subclinical immunodeficiency, to clinical manifestations (e.g., lymphadenopathy), to AIDS. Comparison of these cohorts has shown that full-blown AIDS develops in 8-34% of HTLV-III/LAV positive individuals over 3 years of follow-up. Low T-helper cell counts are predictive of AIDS risk while no strong cofactors for modifying AIDS risk over infected have been detected so far. These results provide the foundation for undertaking in-depth analytic studies of these retrovirus exposure variables to better quantify these risks and the cofactors which determine the clinical outcome of exposure.